title: Larotaxel with Cisplatin in the first-line treatment of locally advanced/metastatic urothelial tract or bladder cancer: a randomized, active-controlled, phase III trial (CILAB).
abstract: BACKGROUND
  This open-label, randomized phase III trial evaluated larotaxel/cisplatin versus gemcitabine/cisplatin as first-line treatment for locally advanced (T4b) or metastatic urothelial tract or bladder cancer.
  
  
  METHODS
  Patients were randomized to larotaxel 50 mg/m(2) with cisplatin 75 mg/m(2) every 3 weeks (larotaxel/cisplatin) or gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 with cisplatin 70 mg/m(2) on day 1 every 4 weeks (gemcitabine/cisplatin). The primary endpoint was overall survival (OS).
  
  
  RESULTS
  The trial was prematurely closed following the sponsor's decision to stop clinical development of larotaxel (n = 337 randomized). The larotaxel dose was reduced to 40 mg/m(2) and cisplatin to 60 mg/m(2) following a data monitoring committee safety review of the first 97 patients. At the time of analysis, the median OS was 13.7 months [95% confidence interval (CI) 11.2-17.1] with larotaxel/cisplatin and 14.3 months (95% CI 10.5 to not reached) with gemcitabine/cisplatin [hazard ratio (HR) 1.21; 95% CI 0.83-1.76; p = 0.33]. The median progression-free survival (PFS) was 5.6 months (95% CI 4.1-6.2) with larotaxel/cisplatin and 7.6 months (95% CI 6.6-9.1) with gemcitabine/cisplatin (HR 1.67; 95% CI 1.24-2.25). More myelosuppression was observed with gemcitabine/cisplatin.
  
  
  CONCLUSIONS
  There was no difference in OS. Although the trial was closed prematurely, PFS appeared worse with larotaxel/cisplatin, suggesting that larotaxel/cisplatin does not improve outcomes versus cisplatin/gemcitabine.
authors.affiliation: Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy.
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.forename: Iwona A
authors.initials: IA
authors.lastname: Skoneczna
authors.forename: Daniel
authors.initials: D
authors.lastname: Castellano
authors.forename: Christine
authors.initials: C
authors.lastname: Theodore
authors.forename: Normand
authors.initials: N
authors.lastname: Blais
authors.forename: Eric
authors.initials: E
authors.lastname: Voog
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.forename: Frank
authors.initials: F
authors.lastname: Peters
authors.forename: Solenn
authors.initials: S
authors.lastname: Le-Guennec
authors.forename: Linda
authors.initials: L
authors.lastname: Cerbone
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Risse
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Machiels
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011446:Prospective Studies; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000473:pathology*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D003841:Deoxycytidine; D002945:Cisplatin; C531079:larotaxel; D000093542:Gemcitabine